Previous studies showed a correlation between the diagnosis of multiple sclerosis and the presence of vaccinia neutralizing antibody in the cerebrospinal fluid. During the past year we have confirmed and extended these data, demonstrating that the presence of such antibody was poorly correlated with CSF IgG and serum vaccinia antibodies. Future investigations will concentrate on the completion of these studies, and a search for vaccinia antigens in brain and spinal cord. The methods used will include fluorescence microscopy, enzyme-labelled antibody to purified vaccinia antigens, elution of antibody from brain material obtained at autopsy, and attempts to demonstrate cross- reactions between vaccinia and brain antigens.